FDA Releases Guidelines for Physicians Using Investigational Drugs in Emergency Situations

In a recent Manual of Policies and Procedures (MAPP), the FDA laid out the process by which physicians can access an investigational drug for treatment in an individual patient in an emergency situation, both during and after normal business hours.

MAPP Specifics

The MAPP describes the policies and procedures established in the Center for Drug Evaluation and Research (CDER) for managing and processing applications for individual patient expanded access for emergency use (or, emergency investigational new drug applications (EINDs)) for licensed physicians seeking access to an investigational drug for treatment use in an individual patient in an emergency situation, both during and after normal business hours.

Although access to an investigational drug for an individual patient in an emergency situation may be requested and authorized through submission of a protocol for such use by an investigational new drug application (IND) holder to its existing IND, this situation is not common and is not addressed in this MAPP. Most emergency access is requested and authorized through submission of a protocol under a new IND (EIND). This scenario (emergency access requested and allowed under an EIND) is addressed in this MAPP.

Background

On August 13, 2009, FDA published in the Federal Register the final rule “Expanded Access to Investigational Drugs for Treatment Use.” This final rule added subpart I regarding expanded access to investigational new drugs for treatment use into 21 CFR part 312.2:

“This subpart contains the requirements for the use of investigational new drugs and approved drugs where availability is limited by a risk evaluation and mitigation strategy (REMS) when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition. The aim of this subpart is to facilitate the availability of such drugs to patients with serious diseases or conditions when there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the patient’s disease or condition.”

Subpart I describes the requirements for expanded access to an investigational drug for treatment use, including access for individual patients in emergencies. Whereas 21 CFR 312.305 describes the requirements for all expanded access uses, 21 CFR 312.310 specifically describes the requirements unique to individual patient access and 21 CFR 312.310(d) describes the procedures for requesting and authorizing access to an investigational new drug for use in an individual patient in an emergency situation.

As explained in 21 CFR 312.305(c), a patient may obtain access to an investigational drug for treatment use, including in an emergency situation, through a licensed physician. A licensed physician under whose immediate direction an investigational drug is administered or dispensed for an expanded access use is considered an investigator. An individual or entity that submits an expanded access IND is considered a sponsor. A licensed physician under whose immediate direction an investigational drug is administered or dispensed and who submits an IND for expanded access is a sponsor-investigator and must comply with the regulatory requirements for sponsors and investigators.

Policy Specifics

Because of the urgency of the situation, CDER will review requests for EINDs immediately upon receipt. CDER may receive requests for EINDs by telephone, facsimile, or other means of electronic communication, although CDER generally does not monitor facsimile transmissions and electronic communications received during nonbusiness hours. During nonbusiness hours, CDER receives requests for EINDs by telephone through FDA’s Emergency Call Center, which is operational 24 hours a day/7 days a week.

The decision to authorize or deny emergency access will be communicated by telephone. Staff will obtain verbal agreement from the licensed physician who contacts FDA to request an EIND for treatment use in his or her patient to submit all necessary forms and information within 15 working days of FDA authorizing access. As described under 21 CFR 56.104(c), emergency use of an investigational drug is exempt from the requirement of a prospective institutional review board (IRB) review, provided that such emergency use is reported to the IRB within 5 working days of treatment initiation. In general, any subsequent uses of the same investigational drug at the same institution will require prior IRB review and approval.

When, however, prior IRB review and approval is not feasible for a subsequent expanded access emergency use of the same investigational drug at the same institution, FDA will not deny the subsequent request for emergency access because of a lack of prospective IRB review. FDA will advise the sponsor to report the use to his or her IRB within 5 working days of treatment initiation.

The Office of New Drugs (OND) review staff will accept single copies of original IND submissions or subsequent amendments to INDs from physicians who submit individual patient expanded access INDs, including EINDs. And an EIND will be authorized only when there is an emergency that requires the patient to be treated before a written submission to FDA can be made.